Use of calcium supplementation is commonly discussed regarding the side effects of androgen deprivation therapy (ADT). ADT and menopause share the phenomenon of accelerated calcium loss from bones. Numerous studies demonstrate that men who are placed on ADT lose from 2-4% of the calcium in their spine during the first year of therapy. Because of this, and the general phenomenon of low vitamin D levels in all of us who use sunscreens more regularly, we recommend that men take vitamin D and calcium supplements when we start ADT.
The results of calcium loss are an increase in the risk of fracture. For example, in a study published in 2007 on 8577 men with prostate cancer who had similar fracture rates prior to treatment, the use of ADT increased the fracture rate from 14.6% to 18.7% over a 36 month observation period. Critiques of these kinds of studies abound. For example, the men who received ADT had more metastases and poorer health in general. Beyond that, in my patients, there is nothing close to 15% of men whom I follow for 3 years who have clinical fractures. How are these determined? Many times it is due to the increase in bone scans and x-rays which may pick up clinically insignificant fractures. Nevertheless, the fact that women in menopause and men after drug-induced andropause have increased calcium loss and fractures is well-established. It is also true that pharmaceutical companies have come up with effective drugs to combat this phenomenon – notably bisphosphonates (like zoledronic acid) and antibodies (like denosumab). An example in men on leuprolide can be found here. In all of these kinds of studies, the placebo/control groups were given calcium and vitamin D.
A mild controversy in this arena arose when publications pointed out an apparent increase in myocardial infarction in patients receiving calcium supplements. In one such study, evaluation of 5 trials in which calcium and vitamin D supplements were randomly assigned to >8000 patients, there were 143 patients with myocardial infarction among calcium users compared to 111 in those on placebo. This has given rise to the concerns expressed by some patients about the safety of calcium and vitamin D supplementation.
Although I am no expert in this area, there clearly are 100’s if not 1000’s of people who are (or who think they are). Ask them or read all of the literature (and DON’T miss clicking on that link…) you wish and reach your own conclusion. The recommendation for normal healthy adults is about 800IU/day of vitamin D as a supplement. You could start here if your concern is primarily about the heart attack risk. Or if you are most concerned about the fracture risk, start here. It is probably reasonable to know your 25-OH vitamin D level to be sure you aren’t deficient. 1000-2000 units of vitamin D/day seems like a reasonable supplement dose in patients who aren’t deficient. You should probably avoid calcium over-supplemntation if you have a history of kidney stones. Avoiding milk products may make sense (see this blog), so taking 1000-1500 mg calcium carbonate (chewable tums or equivalent) daily seems logical to me in patients on ADT who should probably avoid dairy products anyway.
When I was a kid, my father, having grown up on a farm, was obsessed with having me drink lots of milk. There was a milk delivery service in Chadron, NE, that brought rich, fresh, whole milk to our door, and I recall drinking at least a gallon a week – sometimes twice that. I was told it would “build strong bones and healthy teeth”, especially during my pubertal years, when there is of course a growth spurt that does indeed require more calcium and good nutrition. (Hence the increased height of American children over the past century…)
But there is a dark side to this story. In an article in Medscape today, there is a lovely review of another pathway that stimulates prostate cancer, namely one that involves the PI3K-Akt-mTORC1 pathway. It is way beyond this blog to try and go into this pathway in any detail, but suffice it to say that the authors present a powerful (albeit very long) argument that leucine, a branched chain amino acid found in high concentration in cow’s milk stimulates this pathway and can lead to prostate cancer growth and metastases. I will reproduce here (and without permission….I wonder if that is needed in the blog world…) a couple of the figures that illustrate the point. (note I am not plagiarizing since I give you the link to the original article containing these figures)
This figure illustrates how leucine interacts with the signaling pathways that might lead to prostate cancer or stimulate its growth.
This figure demonstrates the increased consumption of milk products like cheese and milk that have occurred over time in western countries.
The bottom line here is that milk and cheese have a dark side and we should probably curtail our intake, especially in families who have high prostate cancer rates. It would be nice to go into all 250+ articles the authors cite, but trust me, their arguments are very well founded. Too bad, since I love cheese so much !
Like all (or most) prostate cancer docs, I have routinely recommended calcium and vitamin D supplements for men going on androgen deprivation therapy (ADT, “hormone treatment”). The reason for this is that many studies show that men, just like their wives/girlfriends, start losing calcium from their bones as soon as testosterone levels drop – the equivalent of menopause and loss of estrogen in women. Of course, medical history is filled with examples of well-meaning interventions for patients that actually don’t work, even though they seem logical. One of the more commonly cited examples is the Vineberg procedure, in which cardiac surgeons re-routed arteries from the chest wall into the left ventricle in patients with coronary artery disease. Makes a lot of sense – the heart muscle isn’t getting enough blood, resulting in angina, so “fix it”. The problem is that it was never properly studied, and when it was, it didn’t work any better than sham operations in reducing angina. There may have been some benefit, but by the time proper studies were done, bypass grafts had overtaken the approach, and now this has been replaced in many cases by stents.
So back to the Vitamin D and Calcium story. An article appearing this week has suggested that our recommendations for calcium and vitamin D supplements are similarly poorly studied. They make sense, but the author appropriately raises questions as to what we actually know verses what seems logical in this paper in “The Oncologist”:
“CONCLUSIONS: Calcium and vitamin D supplements are widely prescribed to men with prostate cancer undergoing ADT. Whether supplementation of men undergoing ADT with calcium and/or vitamin D results in a higher BMD than in those with no supplementation has not been tested. Available clinical trial data regarding supplemental calcium at 500–1,000 mg/day and vitamin D at 200 –500 IU/day indicate that these regimens are inadequate to prevent BMD loss. Calcium supplements have been implicated in greater risks for cardiovascular disease and advanced prostate cancer. Thus, clinical trials to determine the risk–benefit ratio of calcium and vitamin D supplementation in men undergoing ADT for prostate cancer are urgently needed. Key safety endpoints in such trials should include markers of prostate cancer growth, for example, PSA and PSA velocity, as well as surrogate markers of cardiovascular disease.”
For now, I don’t think I will change my recommendations, and like the articles on coffee drinking, or alcohol intake on heart disease and everything else that goes wrong as we age, there will no doubt be lots of counterpoints. The “vitamin D believers” all will tell us that we need to be taking even more vitamin D and the evidence that vitamin D might slow the development of prostate cancer is reasonably solid. In any case, if you have significant heart disease, this article might be something to discuss with your cardiologist, if not your oncologist.